Numerous studies have demonstrated increased risks of second malignancy among young cancer survivors, largely attributed to radiation therapy (RT). However, due to the long latency required to observe second solid cancers (SC) and the rapid evolution of RT techniques, many estimates of radiation-related SC risks reflect the outcomes of treatment no longer in use. Moreover, there is large variation in the normal tissue exposure among individuals nominally receiving the same form of RT. Consequently, published risks of SC are not generalizable to contemporary HL patients, and conceal substantial differences in risk among individual patients.

Ideally, patient-specific radiation exposure data could be used to prospectively

estimate RT-related SC risk. This approach would have the potential advantage of providing patient-specific SC risk estimates to newly diagnosed patients undergoing treatment, and could aid the development of more effective RT techniques by helping to quantify the reduction in late toxicity expected from changes in RT practice.

This talk will review studies that have applied methods of modeling cancer risk among atomic-bomb survivors to radiation-related second cancer risk among patients receiving RT. Epidemiologic data are emerging regarding dose-risk relationship following RT that suggest that standard radiobiologic models may not apply to the SC risk seen following RT. Advances in imaging and individual-level dosimetric estimation will facilitate the creation of patient-specific estimates of SC risk, however major challenges exist to create estimates with confidence intervals sufficiently narrow to be clinically interpretable, and to integrate predictive models into a contemporary biologic theory of radiation carcinogenesis.